The proposed study is a 5-year competitive renewal of the study, Outcomes of Sleep Disorders in Older Men (MrOS Sleep Study). The MrOS Sleep Study was designed to test several hypotheses regarding consequences of sleep disorders in community-dwelling older, by taking advantage of the established cohort that was enrolled for the Osteoporotic Fractures in Men (MrOS) study. From December 2003 through March 2005, 3135 MrOS participants (> 100% of goal) were enrolled into the ancillary MrOS Sleep Study. Comprehensive and objective assessments of sleep (including overnight in-home polysomnography (PSG), 5-day wrist actigraphy and self-reported measures of sleep quality), adjudication of incident cardiovascular (CVD) events, and other measures including biological specimens were added to the expansive dataset of the MrOS parent study. During the initial cycle, we identified sleep disordered breathing (SDB) and hypoxemia as significant independent predictors of CVD, arrhythmias, mortality and non-spine fractures. We now propose continued follow-up of the MrOS Sleep Study cohort to provide sufficient power to determine risk of specific CVD outcomes and disease-specific mortality associated with SDB, rather than aggregate outcomes (Aim 1). Initial findings will also be extended in the renewal by testing several potential mechanisms for the observed relationships between SDB/hypoxemia and outcomes, including i) biochemical determinants that may elucidate mechanistic pathways; ii) lung function and daytime oxygen saturation levels; and iii) objectively measured sleep duration (Aim 2). We further propose to strengthen several of our cross- sectional findings relating sleep to age-related conditions including frailty, physical and cognitive function, by performing longitudinal assessments of these conditions (Aim 3). Finally, repeat measures of PSG and actigraphy will enable us to characterize patterns of change in sleep characteristics among older men during 5 years of follow-up, and to determine the correlates and consequences of these changes (Aim 4). This rare opportunity to continue follow-up in over 3000 men who participated in the original wave of the MrOS Sleep Study, and to re-examine a subset of the cohort who have already contributed such a wealth of data, will provide new insights into the relationships between SDB and sleep patterns with subsequent morbidity and mortality. PUBLIC HEALTH RELEVANCE: Sleep disorders are very common, particularly in older adults. The proposed renewal of the study, Outcomes of Sleep Disorders in Older Men, will provide new insights into the relationships between sleep disordered breathing, hypoxemia, and sleep patterns (measured comprehensively and objectively) with subsequent risk of morbidity and mortality in a large cohort of community-dwelling older men. Several mechanistic pathways will be explored, in addition to extending follow-up to allow for analysis of more specific CVD outcomes and disease-specific mortality (rather than aggregate outcomes).